The effects of diazinon on lipid peroxidation and antioxidant enzymes in erythrocytes in vitro

Diazinon is one of the most widely used organophosphate insecticides (OPI) in agriculture and public health programs. The aim of this study was to investigate how an OPI, diazinon, affects lipid peroxidation (LPO) and the antioxidant defense system in vitro. For this purpose, two experiments were carried out. In experiment 1, the effects of various concentrations of diazinon on LPO and the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) in erythrocytes were studied. Each diazinon concentration was incubated with a previously prepared erythrocyte samples at +4 degrees C for 0, 60 and 180 min. After incubation, the malondialdehyde (MDA) levels and the activities of SOD, GSH-Px and CAT were determined. In experiment 2, in order to determine the direct effect of diazinon on the activities of SOD, GSH-Px and CAT, the erythrocytes were haemolysed and incubated with the various concentrations of diazinon at +4 degrees C for 0, 60 and 180 min. In experiment 1, MDA levels and the activities of SOD and GSH-Px increased with increasing diazinon concentration and incubation period, but CAT activity remained unchanged. In experiment 2, SOD activity was significantly decreased, and GSH-Px activity was significantly increased. From these results, it can be concluded that in vitro administration of diazinon results in the induction of erythrocyte LPO and changes the activities of antioxidant enzymes, suggesting that reactive oxygen species may be involved in the toxic effects of diazinon.     

Therapeutic plasma exchange for the treatment of thrombotic thrombocytopenic purpura: a retrospective multicenter study.

BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) is a rare disease that is fatal if it is not treated. Therapeutic plasma exchange (TPE) has resulted in excellent remission and survival rates in TTP patients. MATERIAL AND METHODS: We describe our experience with 52 TTP patients treated with TPE during the past eight years (65% of the patients were females; patient median age=34 years, range: 17-73). TPE was carried out 1-1.5 times plasma volume. Fresh frozen plasma (FFP) or cryosupernatant plasma (CSP) was used as the replacement fluid. TPE was performed daily until normalization of serum LDH and recovery of the platelet count to >150 x 10(9)/dL; TPE was then slowly tapered. Clinical, laboratory data, the number of TPE, other given therapy modalities, treatment outcomes and survival rate were evaluated retrospectively. RESULTS: Overall response (OR) and complete response (CR) rates were 77% and 60%, respectively. Response was excellent in 82.8% of the patients with primary TTP among whom 74.2% were CR. Additionally, there were statistical differences in terms of CR rate between patients with primary TTP and secondary TTP (74.2% vs. 29.4%; p=0.005). OR and CR rates were 79% and 57.9% in patients on TPE alone and 75.8% and 60.6% in patients on TPE+prednisolone, respectively (p=1 and p=0.8). Additionally, there were no statistical differences in terms of OR and CR rates between patients on TPE with FFP and CSP (p=0.25 and p=0.16, respectively). The presence of fever and the number of TPE were statistically important factors influencing the probability of response in multivariate logistic regression analysis (p<0.01 and p<0.01, respectively). Additionally, in multivariate Cox's regression analysis, the probability of survival was higher in patients who were responsive to treatment compared to patients who were unresponsive (p<0.001). CONCLUSION: TPE is an effective treatment for primary TTP; however, it may be used as adjunctive therapy for secondary TTP until it is under control. The addition of steroids to TPE had no advantage compared to TPE alone. CSP as replacement fluid is not superior compared to FFP. Fever appears to be a bad prognostic indicator. Therefore, prolonged treatment with TPE may be needed in patients with fever.     

Autoimmune thyroid diseases in patients with chronic fasciolosis

BACKGROUND: The prevalence of autoimmune thyroid diseases and autoantibodies in patients with chronic fasciolosis (CF) was investigated. METHODS: Thyroid function of 32 patients with CF and 72 patients without fasciolosis infection was evaluated biochemically. Thyroid hormones, antithyroglobulin antibodies (TgAb) and antithyroid peroxidase antibodies (TPOAb) were measured. RESULTS: In patients with CF, the prevalences of autoantibodies against thyroid peroxidase and thyroglobulin were 21.9% (7/32) and 15.6% (5/32) respectively. However, thyroid function disorder was identified in only 3 (9.4%) cases. In the control group, TPOAb and TgAb were determined in 2 (2.7%) cases, but no one had thyroid function disorder. The prevalences of thyroid autoantibodies (chi 2: 7.948, p < 0.01) and autoimmune thyroid diseases (chi 2: 4.007, p < 0.05) were significantly higher in the CF group. CONCLUSIONS: The high prevalence of TPOAb and TgAb in CF suggests that patients with CF should be evaluated for autoimmune thyroid disorders at the time of diagnosis and during the follow-up period.     

肾移植术后卡氏肺囊虫肺炎5例回顾性分析

目的:观察肾移植术后卡氏肺囊虫肺炎的发生率及治疗效果。方法:选择2003-01/2005-12在中山市人民医院行肾移植的患者112例,患者均知情同意。按是否使用猪抗人淋巴细胞免疫球蛋白分为2组,基础免疫抑制组(n=68)给予环孢素A/他克莫司 吗替麦考酚酯 强的松;抗体诱导组(n=44)给予猪抗人淋巴细胞免疫球蛋白 环孢素A/他克莫司 吗替麦考酚酯 强的松。两组共发生卡氏肺囊虫肺炎5例,其中基础免疫抑制组2例,抗体诱导组3例。5例患者通过普通抗感染治疗,3～7d病情未见好转,遂行支气管镜活检 深部吸痰培养,尽早明确病原体,指导抗菌治疗。比较两组患者卡氏肺囊虫肺炎的发生率,并观察其治疗效果。结果:5例卡氏肺囊虫肺炎患者全部进入结果分析,无脱落。①5例患者经支气管纤维镜肺组织活检确诊为卡氏肺囊虫肺炎,发生率为4.46%,其中抗体诱导组6.82%(3/44)明显高于基础免疫抑制组2.94%(2/68)。②5例卡氏肺囊虫肺炎中2例合并金黄色葡萄球菌感染。以复方磺胺甲恶唑为基础药物进行综合治疗,3例患者临床治愈出院,随访3个月,移植肾及肺功能正常;死亡2例。③5例患者治疗期间均无排斥反应发生。④在发病初期5例患者的CD4/CD8平均值为1.02±0.15,3例治愈患者的CD4/CD8平均值为1.42±0.23,在恢复过程中逐渐升高。2例死亡患者的CD4/CD8平均值为1.10±0.21。结论:早期支气管纤维内镜活检对肾移植术后卡氏肺囊虫肺炎的诊断非常重要,早期诊断、早期治疗是治愈的关键。猪抗人淋巴细胞免疫球蛋白可增加肾移植术后卡氏肺囊虫肺炎的发生率。     

The effect of budesonide mouthwash on oral chronic graft versus host disease

Oral chronic graft versus host disease (cGVHD) is common and a major cause of morbidity and loss of quality of life in long term survivors. Cyclosporine with prednisone remains the first line therapy for oral manifestations of cGVHD. However, even with routine administration of systemic agents, many patients with oral manifestations of cGVHD do not have resolution of their disease and may benefit from incorporation of local therapy. Budesonide is a highly potent steroid which has minimal systemic side effects and being used for oral cGVHD. We designed a retrospective study to compare treatment results of patients with oral cGVHD who received topical budesonide in addition to systemic therapy that consists of combined prednisone and cyclosporine (Group A, n = 12), with the treatment results of patients who were administered the same systemic therapy alone (Group B, n = 11) to determine whether budesonide mouthwash had any advantage on response rates. Three mg topical budesonide/10 ml saline was used 3-4 times a day for up to 6 months in group A. Diagnosis, clinical staging, and treatment response scoring for cGVHD were performed according to National Institutes of Health (NIH) consensus criteria. At the baseline examination, there were no statistically significant differences in terms of median oral cGVHD examination scores between two groups. After treatment, there was statistically significant decrease in median oral cGVHD examination scores compared to baseline (P < 0.001 and 0.021), and significant differences were found between two groups (P < 0.032). Overall response rate was 83% and 36% for group A and B, respectively (P = 0.036). However, no statistically significant differences were found between median pain scores of two groups before and after treatment (P = 0.740 and P = 0.091). No major systemic side effects and oral candidiasis were observed in two groups of patients. We concluded that topical budesonide might be added to systemic therapy to obtain better response rates in patients with oral cGHVD.     

The Effect of <Emphasis Type="Italic">N</Emphasis>ω-Nitro-<Emphasis Type="SmallCaps">l</Emphasis>-Arginine Methyl Ester and <Emphasis Type="SmallCaps">l</Emphasis>-Arginine on Lung Injury Induced by Abdominal Aortic Occlusion–Reperfusion

Purpose

The aim of this study was to examine the effects of Nω-nitro-l-arginine methyl ester (l-NAME) and l-arginine on lung injury after aortic ischemia–reperfusion (IR).

Methods

Twenty-four Wistar-Albino rats were randomized into four groups (n = 6) as follows: Control (sham laparotomy), Aortic IR (30?min ischemia and 120?min reperfusion), l-Arginine (intraperitoneal 100?mg?kg<συπ>?1 live weight)+aortic IR, and l-NAME (intraperitoneal 10?mg?kg<συπ>?1 live weight)+aortic IR. In the lung specimens, the tissue levels of malondialdehyde (MDA), vascular endothelial growth factor (VEGF), and nitric oxide (NO) were measured and a histological examination was done.

Results

Aortic IR increased MDA, VEGF, and NO. l-Arginine further significantly increased MDA and NO, and decreased VEGF (P < 0.05 vs aortic IR). l-NAME significantly decreased MDA and NO (P < 0.05 vs l-arginine+aortic IR) and increased VEGF (P < 0.05 vs other groups). A histological examination showed the aortic IR to significantly increase (P < 0.05 vs control) while l-arginine also further increased (P > 0.05 vs aortic IR), whereas l-NAME caused a significant decrease in pulmonary leukocyte infiltration (P < 0.05 vs aortic IR).

Conclusions

Our results indicate that l-arginine aggravates the lung injury induced by aortic IR, while l-NAME attenuates it.

     

Lower urinary tract phenotype of experimental autoimmune cystitis in mouse: a potential animal model for interstitial cystitis

OBJECTIVE

To examine bladder function in a newly developed experimental autoimmune cystitis (EAC) model in female SWXJ strain mice, as a potential animal model for interstitial cystitis (IC).

MATERIALS AND METHODS

In all, 20 SWXJ female mice were divided into two groups: an EAC group immunized with mouse bladder homogenate in complete Freund’s adjuvant (CFA) and a control group immunized with CFA alone. At 4 months after injection, the bladder function of some mice (six) was studied with 24‐h micturition habits using metabolic cages and conscious cystometrography (CMG). The bladder and lung were harvested for histological examination and to assess interferon‐γ (IFN‐γ) mRNA expression.

RESULTS

Histology examination showed obviously thickened lamina propria, infiltration of lymphocytes, giant cells, and increased mast cells in the detrusor muscle of the EAC mice. The lungs of EAC mice showed normal histology. The IFN‐γ mRNA expression increased significantly in the bladder, but not in the lung of the EAC mice. The 24‐h micturition habits measurements showed increased frequency of urination in the EAC mice compared with the controls. Similarly, CMG showed decreased intercontraction intervals and voided volumes per micturition in the EAC mice compared with the controls. However, there were no significant differences in peak voiding pressure or total voiding volume between the EAC and control mice.

CONCLUSIONS

Our murine EAC model has comparable functional and histological alterations to those seen in human IC, and may provide a useful model for the study of the pathogenesis and treatment of IC.     

Overexpression of cyclooxygenase-2 in multiple myeloma: association with reduced survival

Cyclooxygenases (COX) are key enzymes in the conversion of arachidonic acid to prostaglandins. Several studies have shown a relation between angiogenesis and COX-2 expression. Elevated expression of cyclooxygenase-2 (COX-2), however, has not been reported in multiple myeloma (MM) in the literature. The aim of this study is to investigate COX-2 expression in MM as well as its correlation with prognostic factors and estimated survival rates. Immunohistochemical staining of the paraffin-embedded bone marrow biopsy tissues (n = 51) was performed using isoform-specific COX-2 polyclonal antisera (Santa Cruz Biotechnology, Santa Cruz, CA). Results were correlated with recognized clinical parameters, which were retrospectively obtained from patients' files. There were 15, 19, and 17 bone marrow biopsy specimens with negative, weak-moderate, and strong COX-2 immunostaining, respectively. According to univariate analysis, beta2-microglobulin, age, stage, COX-2 expression, and serum lactate dehydrogenase levels were significant prognostic factors for survival in patients with multiple myeloma. COX-2 expression, age, and serum lactate dehydrogenase levels (greater than 1x normal level) were significant prognostic factors by multivariate analysis. Kaplan-Meier overall survival estimate of those patients with negative or weak-moderate COX-2 immunoreactivity in myeloma cells was significantly better than that of patients with strong COX-2 immunoreactivity (log-rank chi(2) = 21,43, P < 0.001). COX-2 overexpression was associated with reduced estimated survival. Poor prognostic factors such as LDH, age, and beta2-microglobulin were also correlated with COX-2 expression. Potent, specific COX-2 inhibitors showing evident antiangiogenic and antitumor effects on cancers could provide new therapeutic strategies in the treatment of MM.